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overall survival lapatinib breast cancer

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https://www.readbyqxmd.com/read/28810186/the-efficacy-of-lapatinib-and-capecitabine-in-her-2-positive-breast-cancer-with-brain-metastases-a-systematic-review-and-pooled-analysis
#1
REVIEW
Fausto Petrelli, Michele Ghidini, Veronica Lonati, Gianluca Tomasello, Karen Borgonovo, Mara Ghilardi, Mary Cabiddu, Sandro Barni
INTRODUCTION: Breast cancer (BC) with HER-2/neu overexpression or amplification (HER-2+) is associated with a higher prevalence of brain metastases (BMs) when compared to other subtypes. Among approved drugs for HER-2+ BC, lapatinib (L) is associated with single agent activity toward BMs. We conducted a systematic review to determine the efficacy of L, singly or in combination with capecitabine (C), as a treatment for HER-2+ BMs. MATERIAL AND METHODS: We searched PubMed, EMBASE, The Cochrane Library, SCOPUS, Web of Science, ClinicalTrials...
August 12, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28750133/role-of-cytotoxic-tumor-infiltrating-lymphocytes-in-predicting-outcomes-in-metastatic-her2-positive-breast-cancer-a-secondary-analysis-of-a-randomized-clinical-trial
#2
Shuzhen Liu, Bingshu Chen, Samantha Burugu, Samuel Leung, Dongxia Gao, Shakeel Virk, Zuzana Kos, Wendy R Parulekar, Lois Shepherd, Karen A Gelmon, Torsten O Nielsen
Importance: Accumulating evidence indicates that tumor-infiltrating lymphocytes (TILs) are associated with clinical outcomes and may predict the efficacy of chemotherapy and human epidermal growth factor receptor 2 (HER2, encoded by the gene ERBB2)-targeted therapy in patients with HER2-positive breast cancer. Objective: To investigate the role of TILs, particularly cytotoxic CD8+ T cells, in the prediction of outcomes in patients with HER2-positive metastatic breast cancer randomized to an antibody-based (trastuzumab) vs a small molecule-based (lapatinib) anti-HER2 therapy...
July 27, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28670138/sr-b1-targeted-nanodelivery-of-anti-cancer-agents-a-promising-new-approach-to-treat-triple-negative-breast-cancer
#3
Rebecca Johnson, Nirupama Sabnis, Xiangle Sun, Ruhani Ahluwalia, Andras G Lacko
Patients with triple-negative breast cancer (TNBC) have a considerably less favorable prognosis than those with hormone-positive breast cancers. TNBC patients do not respond to current endocrine treatment and have a 5-year survival prognosis of <30%. The research presented here is intended to fill a void toward the much needed development of improved treatment strategies for metastatic TNBC. The overall goal of this research was to evaluate the effectiveness of reconstituted high-density lipoprotein (rHDL) nanoparticles (NPs) as delivery agents for anti-TNBC drugs...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28526538/trastuzumab-emtansine-versus-treatment-of-physician-s-choice-in-patients-with-previously-treated-her2-positive-metastatic-breast-cancer-th3resa-final-overall-survival-results-from-a-randomised-open-label-phase-3-trial
#4
Ian E Krop, Sung-Bae Kim, Antonio Gonzalez Martin, Patricia M LoRusso, Jean-Marc Ferrero, Tanja Badovinac-Crnjevic, Silke Hoersch, Melanie Smitt, Hans Wildiers
BACKGROUND: In the randomised, parallel assignment, open-label, phase 3 TH3RESA study, progression-free survival was significantly longer with trastuzumab emtansine versus treatment of physician's choice in previously treated patients with HER2-positive advanced breast cancer. We report results from the final overall survival analysis of the TH3RESA trial. METHODS: Eligible patients for the TH3RESA trial were men and women (aged ≥18 years) with centrally confirmed HER2-positive advanced breast cancer previously treated with both trastuzumab and lapatinib (advanced setting) and a taxane (any setting) and with progression on two or more HER2-directed regimens in the advanced setting...
June 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28526536/trastuzumab-emtansine-versus-capecitabine-plus-lapatinib-in-patients-with-previously-treated-her2-positive-advanced-breast-cancer-emilia-a-descriptive-analysis-of-final-overall-survival-results-from-a-randomised-open-label-phase-3-trial
#5
Véronique Diéras, David Miles, Sunil Verma, Mark Pegram, Manfred Welslau, José Baselga, Ian E Krop, Kim Blackwell, Silke Hoersch, Jin Xu, Marjorie Green, Luca Gianni
BACKGROUND: The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial. METHODS: EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane...
June 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28415567/efficacy-and-safety-of-t-dm1-in-the-common-practice-of-her2-advanced-breast-cancer-setting-a-multicenter-study
#6
Alessandra Fabi, Michelino De Laurentiis, Michele Caruso, Enrichetta Valle, Luca Moscetti, Daniele Santini, Katia Cannita, Luisa Carbognin, Mariangela Ciccarese, Rosalba Rossello, Grazia Arpino, Vita Leonardi, Filippo Montemurro, Nicla La Verde, Daniele Generali, Alberto Zambelli, Giuseppa Scandurra, Michelangelo Russillo, Ida Paris, Anna Maria D'Ottavio, Gianfranco Filippelli, Marianna Giampaglia, Simonetta Stani, Agnese Fabbri, Daniele Alesini, Daniela Cianniello, Diana Giannarelli, Francesco Cognetti
Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this 'field-practice' study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28376188/regional-nodal-irradiation-after-breast-conserving-surgery-for-early-her2-positive-breast-cancer-results-of-a-subanalysis-from-the-altto-trial
#7
RANDOMIZED CONTROLLED TRIAL
Isabelle Gingras, Eileen Holmes, Evandro De Azambuja, David H A Nguyen, Miguel Izquierdo, Jo Anne Zujewski, Moshe Inbar, Bjorn Naume, Gianluca Tomasello, Julie R Gralow, Antonio C Wolff, Lyndsay Harris, Michael Gnant, Alvaro Moreno-Aspitia, Martine J Piccart, Hatem A Azim
Background: Two randomized trials recently demonstrated that regional nodal irradiation (RNI) could reduce the risk of recurrence in early breast cancer; however, these trials were conducted in the pretrastuzumab era. Whether these results are applicable to human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with anti-HER2-targeted therapy is unknown. Methods: This retrospective analysis was performed on patients with node-positive breast cancer who were enrolled in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization phase III adjuvant trial and subjected to BCS...
August 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28375706/impact-of-diabetes-insulin-and-metformin-use-on-the-outcome-of-patients-with-human-epidermal-growth-factor-receptor-2-positive-primary-breast-cancer-analysis-from-the-altto-phase-iii-randomized-trial
#8
RANDOMIZED CONTROLLED TRIAL
Amir Sonnenblick, Dominique Agbor-Tarh, Ian Bradbury, Serena Di Cosimo, Hatem A Azim, Debora Fumagalli, Severine Sarp, Antonio C Wolff, Michael Andersson, Judith Kroep, Tanja Cufer, Sergio D Simon, Pamela Salman, Masakazu Toi, Lyndsay Harris, Julie Gralow, Maccon Keane, Alvaro Moreno-Aspitia, Martine Piccart-Gebhart, Evandro de Azambuja
Purpose Previous studies have suggested an association between metformin use and improved outcome in patients with diabetes and breast cancer. In the current study, we aimed to explore this association in human epidermal growth factor receptor 2 (HER2 ) -positive primary breast cancer in the context of a large, phase III adjuvant trial. Patients and Methods The ALTTO trial randomly assigned patients with HER2-positive breast cancer to receive 1 year of either trastuzumab alone, lapatinib alone, their sequence, or their combination...
May 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28349782/hr-her2-breast-cancers-with-growth-factor-receptor-mediated-emt-have-a-poor-prognosis-and-lapatinib-downregulates-emt-in-mcf-7-cells
#9
Krisha Desai, Radhika Aiyappa, Jyothi S Prabhu, Madhumathy G Nair, Patrick Varun Lawrence, Aruna Korlimarla, Anupama Ce, Annie Alexander, Rohini S Kaluve, Suraj Manjunath, Marjorrie Correa, B S Srinath, Shekhar Patil, Anjali Kalamdani, Msn Prasad, T S Sridhar
Despite an overall good prognosis, a significant proportion of patients with hormone receptor positive human epidermal growth factor receptor 2 negative breast cancers develop distant metastases. The metastatic potential of epithelial cells is known to be regulated by tumor-stromal interaction and mediated by epithelial-to-mesenchymal transition. Hormone receptor positive human epidermal growth factor receptor 2 negative tumors were used to estimate markers of epithelial-to-mesenchymal transition, and the luminal breast cancer cell line MCF-7 was used to examine the interactions between integrins and growth factor receptors in causation of epithelial-to-mesenchymal transition...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28289045/efficacy-and-safety-of-lapatinib-and-trastuzumab-for-her2-positive-breast-cancer-a-systematic-review-and-meta-analysis-of-randomised-controlled-trials
#10
Zhi-Qiao Xu, Yan Zhang, Ning Li, Pei-Jie Liu, Ling Gao, Xin Gao, Xiao-Jing Tie
OBJECTIVES: The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour actively in models of HER2-positive breast cancer. However, the efficacy of trastuzumab in combination with lapatinib remains controversial. Therefore, we conducted this meta-analysis to compare combination treatment with lapatinib and trastuzumab to trastuzumab or lapatinib alone in the treatment of HER2-positive breast cancer...
March 13, 2017: BMJ Open
https://www.readbyqxmd.com/read/28158234/yes1-signaling-mediates-the-resistance-to-trastuzumab-lap-atinib-in-breast-cancer
#11
Tatsuaki Takeda, Hiromasa Yamamoto, Hirotaka Kanzaki, Ken Suzawa, Takahiro Yoshioka, Shuta Tomida, Xiaojiang Cui, Ramachandran Murali, Kei Namba, Hiroki Sato, Hidejiro Torigoe, Mototsugu Watanabe, Kazuhiko Shien, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Yoshihisa Kitamura, Shinichiro Miyoshi, Toshiaki Sendo, Shinichi Toyooka
BACKGROUND: Overexpression of human epidermal growth factor receptor 2 (HER2) is observed in approximately 15-23% of breast cancers and these cancers are classified as HER2-positive breast cancer. Trastuzumab is the first-line targeted therapeutic drug for HER2-positive breast cancer and has improved patient overall survival. However, acquired resistance to trastuzumab is still a critical issue in breast cancer treatment. We previously established a trastuzumab-resistant breast cancer cell line (named as BT-474-R) from a trastuzumab-sensitive HER2-amplified cell line BT-474...
2017: PloS One
https://www.readbyqxmd.com/read/28152812/real-world-treatment-patterns-and-outcomes-in-her2-positive-mbc-patients-with-brain-metastasis-in-the-u-s-community-oncology-setting
#12
Eileen Fonseca, Bongin Yoo, Thomas Wilson, Hans-Peter Goertz, Catherine Lai
92 Background: Patients (pts) with HER2 positive (HER2+) metastatic breast cancer (MBC) have different patterns of disease and treatment (tx) from HER2 negative MBC. Brain metastasis (BM) frequently occurs and txs vary. METHODS: This retrospective study included adult HER2+ MBC pts from a community oncology network electronic health record (EHR) database and diagnosed between 2009-2011, with follow-up until 11/2014. Pts with other primary tumors were excluded. Two cohorts were defined: pts diagnosed with BM and pts with no evidence of BM (NBM), and were initially matched on age and performance status at MBC diagnosis (dx) and stage...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27866067/escalating-and-de-escalating-treatment-in-her2-positive-early-breast-cancer
#13
REVIEW
Heikki Joensuu
The current standard adjuvant systemic treatment of early HER2-positive breast cancer consists of chemotherapy plus 12months of trastuzumab, with or without endocrine therapy. Several trials have investigated modifications of the standard treatment that are shorter and less resource-demanding (de-escalation) or regimens that aim at dual HER2 inhibition or include longer than 12months of HER2-targeted treatment (escalation). Seven randomized trials investigate shorter than 12months of trastuzumab treatment duration...
January 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27737436/association-of-proton-pump-inhibitors-and-capecitabine-efficacy-in-advanced-gastroesophageal-cancer-secondary-analysis-of-the-trio-013-logic-randomized-clinical-trial
#14
Michael P Chu, J Randolph Hecht, Dennis Slamon, Zev A Wainberg, Yung-Jue Bang, Paulo M Hoff, Alberto Sobrero, Shukui Qin, Karen Afenjar, Vincent Houe, Karen King, Sheryl Koski, Karen Mulder, Julie Price Hiller, Andrew Scarfe, Jennifer Spratlin, Yingjie J Huang, Saba Khan-Wasti, Neil Chua, Michael B Sawyer
Importance: Capecitabine is an oral cytotoxic chemotherapeutic commonly used across cancer subtypes. As with other oral medications though, it may suffer from drug interactions that could impair its absorption. Objective: To determine if gastric acid suppressants such as proton pump inhibitors (PPIs) may impair capecitabine efficacy. Design, Setting, and Participants: This secondary analysis of TRIO-013, a phase III randomized trial, compares capecitabine and oxaliplatin (CapeOx) with or without lapatinib in 545 patients with ERBB2/HER2-positive metastatic gastroesophageal cancer (GEC); patients were randomized 1:1 between CapeOx with or without lapatinib...
June 1, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/27697983/advances-in-systemic-therapy-for-metastatic-or-advanced-gastric-cancer
#15
Kohei Shitara, Atsushi Ohtsu
In recent years, various new agents have been investigated for the treatment of advanced gastric cancer (AGC). The anti-HER2 antibody trastuzumab has been shown to prolong the overall survival of patients with HER2-positive AGC and has become a standard treatment. However, lapatinib, or ado-trastuzumab emtansine (T-DM1), did not show survival benefit in AGC, although it has shown remarkable efficacy for HER2-positive breast cancer. The efficacy of the anti-vascular endothelial growth factor receptor monoclonal antibody ramucirumab for pretreated gastric cancer is a milestone for antiangiogenic therapy for AGC...
October 2016: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/27572338/cost-effectiveness-analysis-of-trastuzumab-emtansine-t-dm1-in-human-epidermal-growth-factor-receptor-2-her2-positive-advanced-breast-cancer
#16
Quang A Le, Yuna H Bae, Jenny H Kang
PURPOSE: The EMILIA trial demonstrated that trastuzumab emtansine (T-DM1) significantly increased the median profession-free and overall survival relative to combination therapy with lapatinib plus capecitabine (LC) in patients with HER2-positive advanced breast cancer (ABC) previously treated with trastuzumab and a taxane. We performed an economic analysis of T-DM1 as a second-line therapy compared to LC and monotherapy with capecitabine (C) from both perspectives of the US payer and society...
October 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27338847/human-epidermal-growth-factor-antagonists-and-cardiotoxicity-a-short-review-of-the-problem-and-preventative-measures
#17
REVIEW
A Dias, W Claudino, R Sinha, C A Perez, D Jain
The Human Epidermal growth factor Receptor 2 (HER2) is a potent mediator of cellular growth and proliferation. It plays an important role in cardiac development and maintaining the physiologic function of an adult heart. Amplification of the HER2 gene, and the corresponding overexpression of the HER2 receptor, occurs in roughly 20% of breast tumors and is associated with a poor outcome. Molecular targeting of the HER2 receptor with the humanized monoclonal antibody, Trastuzumab has improved disease-free and overall survival in patients with both metastatic and early HER2-positive breast cancer...
August 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27224517/predictive-factors-of-lapatinib-and-capecitabine-activity-in-patients-with-her2-positive-trastuzumab-resistant-metastatic-breast-cancer-results-from-the-italian-retrospective-multicenter-herlapac-study
#18
MULTICENTER STUDY
Stefania Gori, Alessandro Inno, Valentina Rossi, Monica Turazza, Elena Fiorio, Alessandra Fabi, Giancarlo Bisagni, Jennifer Foglietta, Daniele Santini, Ida Pavese, Arianna Pellegrino, Alberto Zambelli, Patrizia Vici, Vita Leonardi, Sandro Barni, Silvana Saracchini, Giuseppe Bogina, Fabiana Marchetti, Simona Duranti, Gianluigi Lunardi, Filippo Montemurro
BACKGROUND: There are no validated predictive markers for lapatinib and capecitabine in patients with trastuzumab-resistant HER2 positive metastatic breast cancer. METHODS: Data of 148 consecutive patients treated with lapatinib and capecitabine from March 2007 to December 2013 were collected from 13 Italian institutions. Estimates of progression-free survival (PFS) and overall survival (OS) were obtained with the Kaplan-Meier method and compared with logrank test...
2016: PloS One
https://www.readbyqxmd.com/read/27218867/central-nervous-system-involvement-in-breast-cancer-patients-is-the-therapeutic-landscape-changing-too-slowly
#19
REVIEW
Caterina Fontanella, Elisa De Carlo, Marika Cinausero, Giacomo Pelizzari, Ilaria Venuti, Fabio Puglisi
Central nervous system (CNS) involvement from breast cancer (BC) has been historically considered a relatively rare event. However, the development of new therapeutic strategies with a better control of extra-cranial disease and a longer overall survival (OS) has determined an increased incidence of brain metastases. Patients with HER2-positive or triple negative BC have higher occurrence of CNS involvement than patients with luminal-like disease. Moreover, after development of brain metastases, the prognosis is highly influenced by biological subtype...
May 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27177864/pik3ca-mutations-are-associated-with-reduced-pathological-complete-response-rates-in-primary-her2-positive-breast-cancer-pooled-analysis-of-967-patients-from-five-prospective-trials-investigating-lapatinib-and-trastuzumab
#20
S Loibl, I Majewski, V Guarneri, V Nekljudova, E Holmes, E Bria, C Denkert, C Schem, C Sotiriou, S Loi, M Untch, P Conte, R Bernards, M Piccart, G von Minckwitz, J Baselga
BACKGROUND: The predictive value of PIK3CA mutations in HER2 positive (HER2+) breast cancer treated with neoadjuvant anti-HER2 and chemotherapy has been reported, but the power for subgroup analyses was lacking. PATIENTS AND METHODS: We combined individual patient data from five clinical trials evaluating PIK3CA mutations and associations with pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Patients received either trastuzumab (T), lapatinib (L) or the combination T/L in addition to a taxane-based chemotherapy...
August 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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